pathology of the liver cholestasis
TRANSCRIPT
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PATHOLOGY OF THE LIVER
CHOLESTASIS• Systemic retention of bilirubin and other solutes
eliminated in bile (e.g. bile salts & cholesterol).
• Results from hepatocellular dysfunction & (intra-or extrahepatic) biliary obstruction .
• c/p: Jaundice, pruritis, skin xanthomas, malabs.
• Lab: Elevated bilirubin, alk. phosphatase, lipids .
• Bx: bile pigment accumulation, foamy degenerat-ion, bile duct distension & proliferation, bile lakes, portal tract fibrosis, hepatocytes degeneration and necrosis , cholangitis & cholangiolitis .
• Types:
– Intrahepatic
– Extrahepatic
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PATHOLOGY OF
CHOLESTASIS
1. Accumulation of bile pigment within hepatic parenchyma
2. Hepatocyte swelling and foamy degeneration & necrosis .
3. Bile duct proliferation secondary to biliary tree
obstruction
4. Hepatocyte necrosis, bile lakes, & portal tract fibrosis
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PEDIATRIC LIVER DISEASES
NEONATAL CHOLESTASIS• Prolonged conjugated hyperbilirubinemia in the newborn
• Major causes: EHBA & neonatal hepatitis
– Bile duct obstruction: Extrahepatic biliary atresia(EHBA)
– Neonatal infections: CMV, sepsis, UTI, syphilis
– Toxic: drugs, parenteral nutrition
– Metabolic diseases: tyrosinemia, Niemann-Pick disease, galactosemia, AAT deficiency, cystic fibrosis, ..
– Miscellaneous: shock, hypoperfusion, Alagille’ssyndrome (paucity of bile ducts), ..
– Idiopathic neonatal hepatitis
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PEDIATRIC LIVER DISEASES
NEONATAL CHOLESTASIS
• Clinical presentation is typical: jaundice, dark urine, light stools, hepatomegaly
• Neonatal hepatitis may be primary (idiopathic) or secondary
1. Idiopathic neonatal hepatitis (50-60%).
2. Extrahepatic biliary atresia (20%) .
3. AAT deficiency (15%) .
• Distinction between these disorders is essential because management is different
• Liver biopsy is important in the diagnosis
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HEPATIC FAILURE• Mostly due to progressive, or less often sudden
massive hepatic destruction with erosion of 80-90% of hepatic functional capacity .
• Causes:– 1) Chronic liver disease (acute or chronic failure):
chronic active hepatitis and most types of cirrhosis
– 2) Massive hepatic necrosis (fulminant failure): viral hepatitis, drug & chemical toxicity (acetaminophen, halothane, rifampicin, INH, MOI antidepressants, CCl4, Amanita mushroom toxins
– 3) Hepatic dysfunction without overt necrosis: viable but nonfunctional hepatocytes, e.g. Reye’s syndrome,
tetracycline toxicity, acute fatty liver of pregnancy .
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. Clinical Consequences of Liver Disease
Characteristic signs Hepatic dysfunction:
•Jaundice and cholestasis
•Hypoalbuminemia
•Hyperammonemia
•Hypoglycemia
•Fetor hepaticus
•Palmar erythema
•Spider angiomas
•Hypogonadism
•Gynecomastia
•Weight loss
•Muscle wasting
Portal hypertension from cirrhosis:
•Ascites
•Splenomegaly
•Hemorrhoids
•Caput medusae-abdominal skin
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Life-threatening
complications •Hepatic failure
•Multiple organ failure
•Coagulopathy
•Hepatic encephalopathy
•Hepatorenal syndrome
•Portal hypertension from cirrhosis
•Esophageal varices, risk of
rupture
•Malignancy with chronic disease
•Hepatocellular carcinoma
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HEPATIC FAILURE
• Most cases are due to overwhelming viral hepatitis and alcoholic liver disease .
• Symptoms may occur within days with or without prior history of liver disease .
• A variety of stressful events may contribute to onset of failure:
– GI bleeding
– Acute infections
– Electrolyte disturbances
– Major surgery, heart failure, shock
• Treatment: not satisfactory
• Px: 80% mortality rate
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HEPATIC ENCEPHALOPATHY• A metabolic disorder of CNS & neuromuscular
system associated with severe loss of hepatocellular function & portosystemic shunting
• The brain is exposed to an altered metabolic environment (ammonia?) which impairs neuronal function & promotes generalized brain edema .
• Patients exhibit a wide range of disturbances of consciousness: subtle behavioural changes, confusion, stupor, deep coma & death .
• Other neurologic signs: Rigidity, hyperreflexia, EEG changes, seizures, asterixis
• Minor morphologic changes in brain
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HEPATO-RENAL SYNDROME
• Development of renal failure in patients with severe liver disease, without presence of intrinsic morphologic or functional causes in the kidney.
• Excluded are cases of concomitant damage to liver & kidneys and acute tubular necrosis secondary to circulatory collapse .
• Pathogenesis: due to Vascular collapse and decreased renal blood flow ?
• c/p: decrease in urine output .
• Retained ability to concentrate urine . Hyperosmolar urine, protein -ve & low Na
+ .
• Lab: Increased blood urea and creatinin .
• Px: May hasten death or may persist for months
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CIRRHOSIS
• Irreversible end stage of chronic liver disease,
which leads to parenchymal injury and fibrosis
• 3 histologic features:
1. Disruption of entire liver architecture
2. Bridging fibrous septa
3. Parenchymal nodules
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ETIOLOGIC CLASSIFICATION OF
CIRRHOSIS1. Viral hepatitis
2. Alcoholic liver disease
3. Biliary diseases
4. Genetic hemochromatosis
5. Wilson’s disease
6. a1-antitrypsin deficiency
7. Drugs (a-methyldopa, acetaminophen…)
8. Syphilis
9. Galactosemia, tyrosinosis..
10. “Cardiac cirrhosis”
11.Cryptogenic cirrhosis